Improved Hemodynamic Recovery and 72-Hour Survival Following Low-Volume Resuscitation with a PEGylated Carboxyhemoglobin in a Rat Model of Severe Hemorrhagic Shock

Antoni Macko, Forest R Sheppard, William H Nugent, Abe Abuchowski, Bjorn K Song

Mil Med 2020 Aug 14;185(7-8):e1065-e1072

Introduction: Hemorrhage is a leading cause of death from potentially survivable civilian and military trauma. As projected conflicts move from settings of tactical and logistical supremacy to hyper-dynamic tactical zones against peer and near-peer adversaries, protracted medical evacuation times are expected. Treatment at the point-of-injury is critical. Although crystalloids like Lactated Ringer's (LR) are ubiquitous, whole blood (WB) is the preferred resuscitation fluid following hemorrhage; however, logistical constraints limit the availability of WB in prehospital settings. Hemoglobin-based oxygen carriers (HBOCs) offer both hemodynamic support and oxygen-carrying capacity while avoiding logistical constraints of WB. We hypothesized that low- volume resuscitation of severe hemorrhagic shock with an HBOC (PEGylated carboxyhemoglobin, [PC]) would improve hemodynamic recovery and 72-hour survival; comparable to WB and superior to LR.

Materials and methods: A total of 21 anesthetized male Sprague-Dawley rats underwent severe hemorrhagic shock followed by randomly assigned low-volume resuscitation with LR, WB, or PC, and then recovered from anesthesia for up to 72-hour observation. Mean arterial pressure (MAP) was recorded continuously under anesthesia, and arterial blood gases were measured at baseline (BL), 60 minutes post-hemorrhage (HS1h), and 24 hours post- resuscitation (PR24h). Survival was presented on a Kaplan-Meier plot and significance determined with a log-rank test. Cardiovascular and blood gas data were assessed with one- way analysis of variance and post hoc analysis where appropriate.

Results: All measured cardiovascular and blood chemistry parameters were equivalent between groups at BL and HS1h. BL MAP values were 90 ± 3, 86 ± 1, and 89 ± 2 mmHg for LR, PC, and WB, respectively. Immediately following resuscitation, MAP values were 57 ± 4, 74 ± 5, and 62 ± 3 mmHg, with PC equivalent to WB and higher than LR (P < 0.05). WB and LR were both lower than BL (P < 0.0001), whereas PC was not (P = 0.13). The PC group's survival to 72 hours was 57%, which was not different from WB (43%) and higher than LR (14%; P < 0.05).

Conclusions: A single bolus infusion of PC produced superior survival and MAP response compared to LR, which is the standard fluid resuscitant carried by combat medics. PC was not different from WB in terms of survival and MAP, which is encouraging because its reduced logistical constraints make it viable for field deployment. These promising findings warrant further development and investigation of PC as a low-volume, early treatment for hemorrhagic shock in scenarios where blood products may not be available.